Koek W, Colpaert F C, Woods J H, Kamenka J M
Neurobiology Division, FONDAX-Groupe de Recherche Servier, Puteaux, France.
J Pharmacol Exp Ther. 1989 Sep;250(3):1019-27.
Phencyclidine (PCP) inhibits dopamine (DA) uptake and acts as a noncompetitive N-methyl-D-aspartate antagonist by binding to PCP receptors. The PCP analog N-[1-(2-benzo(b)thiophenyl) cyclohexyl]piperidine (BTCP, GK13) is a potent DA uptake inhibitor, but has low affinity for PCP receptors. The behavioral effects of BTCP were compared with those of PCP, ketamine, MK-801 and cocaine. In mice, BTCP, like cocaine, produced locomotion, sniffing and gnawing; haloperidol blocked these effects. PCP, ketamine and MK-801 produced locomotion, sniffing, swaying and falling. PCP, ketamine and MK-801 produced generalization in rats discriminating either cocaine, PCP or MK-801 from saline. Like cocaine, BTCP produced generalization in cocaine-discriminating rats only; haloperidol partially antagonized this effect. In pigeons, PCP-like catalepsy was produced by ketamine and MK-801, but not by BTCP. N-methyl-D-aspartate-induced convulsions in mice were antagonized by PCP, ketamine and MK-801, but not by BTCP or cocaine. Thus, BTCP shared only cocaine-like behavioral effects with PCP, ketamine and MK-801. A DA antagonist reduced the effects of BTCP. Therefore, the cocaine-like behavioral effects of BTCP may be mediated primarily by DA uptake mechanisms. However, PCP receptors, but not DA uptake mechanisms, may mediate the cocaine-like behavioral effects of PCP, ketamine and MK-801, because their order of potency in producing these effects (MK-801 greater than PCP greater than ketamine) is consistent with their potency order at PCP receptors, but not at DA uptake sites.
苯环己哌啶（PCP）抑制多巴胺（DA）摄取，并通过与PCP受体结合而作为一种非竞争性N-甲基-D-天冬氨酸拮抗剂。PCP类似物N-[1-(2-苯并噻吩基)环己基]哌啶（BTCP，GK13）是一种有效的DA摄取抑制剂，但对PCP受体的亲和力较低。将BTCP的行为效应与PCP、氯胺酮、MK-801和可卡因的行为效应进行了比较。在小鼠中，BTCP与可卡因一样，可产生活动、嗅探和啃咬行为；氟哌啶醇可阻断这些效应。PCP、氯胺酮和MK-801可产生活动、嗅探、摇摆和跌倒行为。PCP、氯胺酮和MK-801在能区分可卡因、PCP或MK-801与生理盐水（对照）的大鼠中可产生泛化反应。与可卡因一样，BTCP仅在能区分可卡因的大鼠中产生泛化反应；氟哌啶醇可部分拮抗这一效应。在鸽子中，氯胺酮和MK-801可产生类似PCP的僵住反应，但BTCP不会。PCP、氯胺酮和MK-801可拮抗N-甲基-D-天冬氨酸诱导的小鼠惊厥，但BTCP或可卡因则不能。因此，BTCP仅与PCP、氯胺酮和MK-801具有类似可卡因的行为效应。一种DA拮抗剂可减弱BTCP的效应。因此，BTCP类似可卡因的行为效应可能主要由DA摄取机制介导。然而，PCP受体而非DA摄取机制可能介导PCP、氯胺酮和MK-801类似可卡因的行为效应，因为它们产生这些效应的效力顺序（MK-801＞PCP＞氯胺酮）与其在PCP受体而非DA摄取位点的效力顺序一致。
